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Examining the Health Effects of Fructose
JAMA ^ | June 3, 2013 | David S. Ludwig, MD, PhD

Posted on 06/07/2013 7:29:21 PM PDT by neverdem

In the 1990s, excessive fat consumption was commonly believed to be the main cause of obesity. High sugar consumption was often considered to be innocuous and possibly protective against obesity by displacing dietary fat.1 A decade later, the American Heart Association linked intake of added sugars to weight gain and recommended substantial decreases in consumption to a daily maximum of 100 kcal for women and 150 kcal for men.2 Some experts now argue that sugar comprises the single most important cause of the worldwide epidemics of obesity and diabetes, primarily through the effects of fructose at prevailing levels of consumption.3 This Viewpoint examines the physiological effects of common sugars and argues against a narrow public health focus on fructose.

FRUCTOSE VS GLUCOSE

Fructose, a 6-carbon sugar, is more than twice as sweet as its isomer glucose. Most caloric sweeteners contain approximately equal amounts of these 2 sugars, either linked covalently in sucrose (table sugar) or as monosaccharide mixtures in high-fructose corn syrup and honey. Pure glucose, as found in unmodified corn syrup, has relatively little sweetness, and pure fructose may cause malabsorption in some people, limiting its practical use.

Despite chemical similarities, the metabolism of these 2 sugars differs markedly, and this difference underlies recent health concerns.3 Following consumption, glucose potently stimulates insulin secretion, promoting glycogen synthesis in the liver and glucose uptake by tissues throughout the body. In contrast, fructose does not directly elicit insulin secretion and is taken up almost exclusively by the liver. Moreover, unlike glucose, the metabolism of fructose is not tightly regulated by liver cell energy state. Consequently, fructose rapidly undergoes glycolysis, fueling de novo lipogensis under some conditions. This newly synthesized lipid may accumulate locally, causing fatty liver and hepatic insulin resistance, or be exported, increasing serum triglycerides, systemic insulin resistance, and fat deposition in adipose tissue. Fructose metabolism may also up-regulate hepatic signal transduction pathways involved in inflammation and drive uric acid production, possibly contributing to hypertension and endothelial dysfunction. Consistent with these mechanisms, feeding studies have demonstrated marked metabolic aberrations—including insulin resistance, dyslipidemia, higher blood pressure, and increased visceral adiposity—among obese individuals consuming fructose compared with glucose.3

However, these feeding studies have been criticized for providing unrealistically high amounts of fructose, typically exceeding the 95th percentile of consumption by 50% or more.4 A recent meta-analysis found no adverse effects of isocaloric substitution of fructose and glucose at average consumption levels for body weight, lipids, blood pressure, uric acid, or insulin levels and found possible benefit for glucose tolerance and glycemic control in diabetes.5 The monosaccharide feeding studies have also been criticized because humans virtually always consume fructose together with glucose, as in sucrose, high-fructose corn syrup, or honey, not in isolation.4

Another argument against fructose having uniquely harmful effects involves the glycemic index, a measure of how food affects blood glucose in the postprandial period. Glucose and most commonly consumed starchy foods (all starches are polymers of glucose) have a high glycemic index, whereas fructose has an exceptionally low value. If the effects of fructose on health predominated, and the various forms of glucose were innocuous, then the glycemic index should have a null or inverse association with disease risk. However, systematic reviews and meta-analyses have linked a high glycemic index diet to the same adverse effects as fructose, including obesity and diabetes.6- 7

In light of these considerations, a critical scientific question is whether replacement of fructose-containing sweeteners at prevailing consumption levels with glucose (as a monosaccharide or as starch) would provide health benefits. If so, a specific public health focus on fructose may be warranted. If not, then broader measures targeting all highly processed carbohydrate foods would be indicated. However, no modern controlled feeding studies adequately address this question, but research dating back to the 1970s is informative. In 1 study, 9 men and women, aged 37 to 62 years, living in a metabolic ward consumed a high-sugar diet (containing 70% of carbohydrate as sucrose, an average of about 675 kcal/d) or a sucrose-free diet (containing wheat and potato starch), each for 4 weeks. Upon repeated measurements, fasting blood glucose was slightly higher (3 mg/dL) for the sucrose condition but no differences between diets were found in body weight, glucose tolerance, fasting and stimulated insulin, cholesterol, triglycerides, or nonesterified fatty acids.8

DIGESTION RATE, NOT DOSE

Fruit is the primary natural source of fructose. Most fruits have about 10 g of fructose, as monosaccharide or sucrose, per 80-kcal serving, comprising at least half the total sugar content. If fructose were toxic at high dosage, then individuals consuming large amounts of fruit might experience adverse effects. However, observational studies report inverse associations between fruit consumption and body weight or risk of obesity-associated diseases, with no evident upper threshold for protection,9 although some studies do not adequately distinguish between fruits and vegetables.

In possibly the only interventional study of its kind, 17 Bantu and white adults in South Africa, aged 20 to 64 years, consuming a Western diet were instructed to eat primarily fruit (20 servings per day for the typical participant) supplemented with nuts to satisfy basic macronutrient requirements.10 Despite the extraordinarily high fructose content of this diet, presumably about 200 g/d, the investigators reported no adverse effects (and possible benefit) for body weight, blood pressure, and insulin and lipid levels after 12 to 24 weeks. Nevertheless, findings from this study must be interpreted cautiously because of important design limitations, including lack of an active control group.

The absence of harm from high fruit consumption likely relates to the slow digestion rate of whole fruit compared for example with a sugar-sweetened beverage, producing portal fructose concentrations that do not exceed hepatic metabolic capacity. Although soluble fiber helps to reduce sugar absorption rates from the digestive tract (primarily by increasing luminal viscosity), the physical form and cellular structure of whole fruit probably have a greater effect, by sequestering sugar away from the absorptive surface of the small intestine. In addition, the high micronutrient and antioxidant content of fruit may protect against hepatic inflammation and systemic insulin resistance.

CONCLUSIONS

Few modern studies have compared the long-term effects of glucose, fructose, and starch under physiologically relevant condition, and such research should assume high priority. The available evidence suggests 3 key points. First, fructose in its primary natural form (whole fruit) is not associated with adverse effects up to the limits of human consumption. Second, excessive intake of refined sugar plays a significant role in the epidemics of obesity and related diseases, in part because large amounts of rapidly absorbed fructose can overwhelm hepatic biochemical pathways. Third, rapidly absorbed forms of glucose—present in both sugar and high glycemic index starch—also contribute importantly to these diseases, especially considering their much greater caloric contribution to typical diets than fructose. Therefore, the recommendation to replace fructose with glucose lacks an evidence basis. Rather, public health efforts should focus on reducing intakes of all highly processed carbohydrates, not just refined sugar.

AUTHOR INFORMATION

Corresponding Author: David S. Ludwig, MD, PhD, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115 (david.ludwig@childrens.harvard.edu).

Published Online: June 3, 2013. doi:10.1001/jama.2013.6562

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving grants from the National Institutes of Health and foundations for obesity-related research, mentoring, and patient care and receiving royalties from a book about childhood obesity.

Funding/Support: Dr Ludwig is supported in part by an endowment from Boston Children's Hospital and career award K24DK082730 from the National Institute of Diabetes and Digestive and Kidney Diseases.

Role of Sponsors: The funders had no role in the preparation, review, or approval of the manuscript or in the decsion to submit the manuscript for publication.

Disclaimer: The content of this article is solely the responsibility of the author and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

Additional Contributions: I thank Marion Nestle, PhD, of New York University, Dariush Mozaffarian, MD, DrPH, and Frank Sacks, MD, of Harvard School of Public Health, Bruce Bistrian, MD, PhD, of Harvard Medical School, and Cara Ebbeling, PhD, of Boston Children's Hospital for providing detailed comments on an earlier version of the manuscript. None of these individuals received compensation for their efforts.

REFERENCES

Hill JO, Prentice AM. Sugar and body weight regulation. Am J Clin Nutr. 1995;62(1):(suppl) 264S-273S
PubMed
Johnson RK, Appel LJ, Brands M, et al; American Heart Association Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism and the Council on Epidemiology and Prevention. Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2009;120(11):1011-1020
PubMed | Link to Article
Lustig RH. Fructose: it's “alcohol without the buzz.” Adv Nutr. 2013;4(2):226-235
PubMed | Link to Article
White JS. Challenging the fructose hypothesis: new perspectives on fructose consumption and metabolism. Adv Nutr. 2013;4(2):246-256
PubMed | Link to Article
Sievenpiper JL.Toronto 3D (Diet, Digestive Tract, and Disease) Knowledge Synthesis and Clinical Trials Unit. Fructose: where does the truth lie? J Am Coll Nutr. 2012;31(3):149-151
PubMed
Ludwig DS. The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA. 2002;287(18):2414-2423
PubMed | Link to Article
Barclay AW, Petocz P, McMillan-Price J, et al. Glycemic index, glycemic load, and chronic disease risk—a meta-analysis of observational studies. Am J Clin Nutr. 2008;87(3):627-637
PubMed
Dunnigan MG, Fyfe T, McKiddie MT, Crosbie SM. The effects of isocaloric exchange of dietary starch and sucrose on glucose tolerance, plasma insulin and serum lipids in man. Clin Sci. 1970;38(1):1-9
PubMed
He FJ, Nowson CA, Lucas M, MacGregor GA. Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: meta-analysis of cohort studies. J Hum Hypertens. 2007;21(9):717-728
PubMed | Link to Article
Meyer BJ, de Bruin EJ, Du Plessis DG, van der Merwe M, Meyer AC. Some biochemical effects of a mainly fruit diet in man. S Afr Med J. 1971;45(10):253-261
PubMed


TOPICS: Culture/Society; Editorial; News/Current Events
KEYWORDS: fructose

1 posted on 06/07/2013 7:29:21 PM PDT by neverdem
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To: neverdem
Thanks for the post. This information has been available since the late 70's. But it has not been accepted by the "medical community."

I detest the "nanny state" and Mike Bloomberg is the worst form of despot that there is. But yes. 25 years practicing medicine has confirmed for me what I knew then. Sugar kills. It's not the government's job to tell you what to eat. Its your job to decide.

2 posted on 06/07/2013 7:43:17 PM PDT by outofstyle (Down All the Days)
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To: neverdem
Thanks, this article makes sense. Glucose is absolutely essential for life, fructose is not. Fructose metabolism produces fat, normal amounts of glucose (from starch) produce glycogen (energy storage) or enter glycolysis for production of ATP. There is a big difference between calories from sugar and calories from starch. I've found this out personally, from years of dieting.
3 posted on 06/07/2013 7:46:58 PM PDT by Huskrrrr
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To: Huskrrrr

I’m with you, I now STAY CLEAR of High Fructose Corn Syrup like the plague. I just feel like an IDIOT for not figuring that out sooner.


4 posted on 06/07/2013 8:06:47 PM PDT by BobL (To us it's a game, to them it's personal - therefore they win.)
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To: neverdem

Ping for later read.


5 posted on 06/07/2013 8:39:39 PM PDT by diamond6 (Behold this Heart which has so loved men!" Jesus to St. Margaret Mary)
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6 posted on 06/07/2013 9:03:54 PM PDT by neverdem (Register pressure cookers! /s)
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To: BobL
I’m with you, I now STAY CLEAR of High Fructose Corn Syrup like the plague. I just feel like an IDIOT for not figuring that out sooner.

Ditto! I used to drink Dr. Pepper like it was going out of style. Haven't had one in well over a year and don't miss it AT ALL. I also avoid anything with Aspertame. It wreaks havoc on your body as well. Originally invented as a pesticide.

7 posted on 06/07/2013 9:19:16 PM PDT by ASouthernGrl (BHO sucks - literally or metaphorically, you decide.)
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To: neverdem

Type of sugar consumed is not important....it’s the dose that makes the poison.


8 posted on 06/07/2013 9:19:50 PM PDT by count-your-change (you don't have to be brilliant, not being stupid is enough)
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To: Huskrrrr
Glucose is absolutely essential for life"

Serum glucose is absolutely essential for life. Dietary glucose is not.

The body is perfectly capable of manufacturing all the glucose it needs from protein and fat.

9 posted on 06/07/2013 10:21:35 PM PDT by jdege
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To: neverdem

I’m a bit suspicious of the fructose is bad, only when you drink it in a soda crowd. I don’t think that anyone has been able to show any chemical difference between fructose in soda and fructose in fruit.

I wonder if we could do any cross-cultural comparisons with countries such as Mexico which have cane sugar in their drinks. As I understand it, the key reason fo HFCS is that American sugar prices are kept unfairly high by legislation which protects cane and beet farmers.


10 posted on 06/07/2013 10:26:48 PM PDT by Fractal Trader
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To: Fractal Trader
I don’t think that anyone has been able to show any chemical difference between fructose in soda and fructose in fruit.

But there's a huge difference in how fast they are absorbed.

Ever been to a BBQ and had four beers over four hours? Sat at a bar and slammed four shots in four minutes? They contain about the same amount of ethanol. The effects are very different.

There's a rate at which the body can process fructose. Eating it as a solid, bound up in fiber, as in fruit, results in an extended period of moderate levels of fructose entering the system. Drinking the same amount as a liquid results in an extremely rapid, extremely high level of fructose. It's not at all inconceivable that this would make a difference.

11 posted on 06/07/2013 10:36:19 PM PDT by jdege
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To: neverdem

I dunno, without my fruit and protein I would keel over. I hit the gym and ride my bike daily. Do they ever put into the argument how much someone moves around? I’m 20% body fat in my 50’s. Fruit, vegetables and protein are an integral part of my diet.


12 posted on 06/08/2013 2:35:32 AM PDT by poobear (Socialism in the minds of the elites, is a con-game for the serfs, nothing more.)
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To: neverdem

I’ve found that my body weight increases substantially based on how much and what type sugar I’m taking in. Fruits and vegetables actually help me maintain a desirable weight. Processed sugars can cause me to gain weight. Corn syrup sugars cause me to gain weight rapidly. I know some people who can scarf down sugars of all types without consequence, but I have to watch my intake.


13 posted on 06/08/2013 2:45:15 AM PDT by whatshotandwhatsnot (Islam Wants You Dead!)
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To: BobL
HFCS

I figured it out over twenty years ago, and was pretty much labelled a conspiracy theorist. At least now it's gotten possible to get food that doesn't have corn syrup in it. A little bit of granulated sugar as an ingredient is fine.

I'm also avoiding added whey and added gluten (I'm okay with the normal amounts that are part of foods). They destroy the natural balance of food. And besides, when you get used to food without these three additives, it tastes much better.

14 posted on 06/08/2013 3:07:34 AM PDT by grania
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To: Fzob

ping...


15 posted on 06/08/2013 5:18:01 AM PDT by Popman (Godlessness is always the first step to the concentration camp.)
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To: ASouthernGrl

” I also avoid anything with Aspertame. It wreaks havoc on your body as well. Originally invented as a pesticide.”

Yea, I heard that too. Freaky stuff. I think the key is how much ‘processing’ (i.e., chemical changes) is done, as human bodies, of which our medical community knows squat about, is not designed to handle them.


16 posted on 06/08/2013 6:10:01 AM PDT by BobL (To us it's a game, to them it's personal - therefore they win.)
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To: grania

I’m with you.


17 posted on 06/08/2013 6:10:32 AM PDT by BobL (To us it's a game, to them it's personal - therefore they win.)
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To: ASouthernGrl
I also avoid anything with Aspertame. It wreaks havoc on your body as well.

Do you know of any studies that have been done on the health effect of aspertame? If so I'd appreciate a heads up

18 posted on 06/08/2013 6:33:15 AM PDT by Castlebar
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To: BobL
FWIW, I buy granulated cane sugar in one teaspoon packets and use that for sweetening cereals and tea/coffee. Two teaspoons is only 30 calories and it provides more sweetening than those calorie or chemical laden ingredients in manufactured foods. Besides that, real cane sugar in that amount actually seems to be a plus for digestion and feeling full and satisfied from foods.

The other thing is cooked plain vegetables. At a buffet, if I can get plain boiled or steamed carrots, brocolli, cabbage, celery and some others, a dish of that as an appetizer is filling, nutritious, and very tasty when your taste buds adjust. Breads or cereals...only 100% whole grain, no added sugar. Instead of butter...a Smart Balance concoction with olive oil. Also, no sauces and no breading. No cooking in butter. The result....I'm an average weight for the first time in my life (I was born 10% overweight) and have never enjoyed food more!

And I still enjoy a good steak dinner, often.

19 posted on 06/08/2013 6:41:29 AM PDT by grania
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To: jdege

Yes, this is true. Is a diet of only protein and fat as healthy as one that includes carobohydrates?


20 posted on 06/08/2013 7:11:23 AM PDT by Huskrrrr
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To: Huskrrrr
Yes, this is true. Is a diet of only protein and fat as healthy as one that includes carobohydrates?

Your body has an indispensable need for glucose/fructose for DNA synthesis and repair and for brain metabolism. If you have no carbohydrates whatsoever in your diet, you can use certain amino acids and other products of the catabolism of fats and proteins to produce glucose through gluconeogenesis.
21 posted on 06/08/2013 7:22:25 AM PDT by aruanan
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To: aruanan

Yes, I know most of the metabolic pathways and how they work, I teach biochemistry in college. My question is what are the long term health effects of a no carb diet (eg heart disease). There seems to be a disagreement among researchers as to the health consequences of a no carb diet. I was wondering what your opinion was on this subject.


22 posted on 06/08/2013 7:30:29 AM PDT by Huskrrrr
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To: grania

“Besides that, real cane sugar in that amount actually seems to be a plus for digestion and feeling full and satisfied from foods.”

Yep, I think there’s something to that...I’ll try it too.


23 posted on 06/08/2013 8:08:48 AM PDT by BobL (To us it's a game, to them it's personal - therefore they win.)
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To: jdege
Eating it as a solid, bound up in fiber, as in fruit, results in an extended period of moderate levels of fructose entering the system.

I don't think anyone has suggested that fruit juice, for example, is as dangerous as HFCS soda, and I have never heard that carbonation, per se, is deleterious to your health.

24 posted on 06/08/2013 8:42:49 AM PDT by Fractal Trader
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To: Fractal Trader
I don't think anyone has suggested that fruit juice, for example, is as dangerous as HFCS soda

Actually, quite a few people have suggested that:

http://articles.mercola.com/sites/articles/archive/2010/06/19/richard-johnson-interview-may-18-2010.aspx

http://drjulindalee.wordpress.com/2013/05/13/what-fruit-juices-fructose-and-low-glycemic-index-really-mean/

25 posted on 06/08/2013 8:56:30 AM PDT by jdege
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To: Huskrrrr

I have no idea what the long term effects are, but for me my cholesterol improved quite a bit as a result of a 45 day no carb regimen.


26 posted on 06/08/2013 9:01:49 AM PDT by csmusaret (Will remove Obama-Biden bumperstickers for $10)
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To: Huskrrrr
There seems to be a disagreement among researchers as to the health consequences of a no carb diet.

Prolonged Meat Diets with a Study of Kidney Function and Ketosis

27 posted on 06/08/2013 9:07:35 AM PDT by jdege
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To: jdege

Interesting. I have been following a blog for the past two years which I have found authoritative on a wide variety of nutrition/obesity subjects, and he has never mentioned fruit juice to date, even though he has covered a wide variety of topics.

An interesting related subject is “de novo lipogenesis,” or the idea that sugar is turned into fat. Lots of research papers suggest that this is impossible, or quite uncommon.

Any way, here’s the link to his blog:

http://wholehealthsource.blogspot.com/


28 posted on 06/08/2013 9:07:54 AM PDT by Fractal Trader
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To: poobear

without my fruit and protein I would keel over.

Stop eating it then....PLEASE!


29 posted on 06/08/2013 10:40:26 AM PDT by napscoordinator (Santorum-Bachmann 2016 for the future of the Country!)
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To: jdege

I had a doctor tell me that I could safely eat cantaloupe but not watermelon because supposedly the watermelon had a much higher fructose content. Having grown up hauling both of them to the market by the pickup load I had an idea he was wrong. A little research confirmed my suspicions, the sugar content varies more between varieties than it does between the average of the two categories, some varieties of cantaloupe have MORE sugar than some watermelons.


30 posted on 06/08/2013 11:45:03 AM PDT by RipSawyer (I was born on Earth, what planet is this?)
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To: jdege

Thanks!


31 posted on 06/08/2013 12:26:42 PM PDT by Huskrrrr
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To: csmusaret

Thanks!


32 posted on 06/08/2013 12:27:04 PM PDT by Huskrrrr
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To: Fractal Trader
Lots of research papers suggest that this is impossible, or quite uncommon.

I'm unaware of any research papers that suggest that de novo lipogenesis is impossible, or that it is uncommon. Quite the contrary. The metabolic pathways exist in every animal species, from bacteria on up. The only question is the rate at which it happens, and whether it is a significant source of fat deposition.

On this, studies are mixed, at least with respect to glucose. There have been a number of studies that suggested that de novo lipogenesis is not a major pathway for most people. Which may be true.

The more important question, in my mind, is whether it becomes a major pathway for those with metabolic syndrome. And they suggest that for that population, DNL is a significant source of fat:

http://ajcn.nutrition.org/content/77/1/43.full

Until recently, DNL was believed to be an insignificant pathway in humans who eat a Western, high-fat diet. In addition, very little was known about the effect of the often recommended alternative diet, which is a low-fat, high-carbohydrate diet, on hepatic metabolism. However, with the development of new methodologies for measuring hepatic DNL, it was shown that hepatic DNL varies greatly depending on the health of the subjects (12, 13, 15) and the types of diets they consume (4, 5, 7, 9–11, 18, 19). The present study sought to answer 3 questions. First, do hyperinsulinemic obese subjects fed a Western, high-fat diet have higher fractional hepatic DNL than do normoinsulinemic lean or obese subjects fed the same diet? Second, is hepatic DNL increased when simple carbohydrate represents 54% of a low-fat, high-carbohydrate diet? And third, what is the relation of increased hepatic DNL to VLDL-triacylglycerol concentrations?

[...]

With the high-fat, low-carbohydrate diet, DNL was minimal and did not differ significantly between the lean and obese subjects with normal fasting insulin concentrations. In contrast, hyperinsulinemic obese subjects had a significantly higher DNL compared with both lean and obese normoinsulinemic subjects (Figure 1⇓; P < 0.05). Interestingly, although DNL did not differ significantly between the lean normoinsulinemic and the obese hyperinsulinemic subjects who consumed the low-fat, high-carbohydrate diet (Figure 1⇓), DNL was significantly higher (P < 0.05) with the low-fat, high-carbohydrate diet for both groups when compared with the normoinsulinemic subjects who consumed a high-fat, low-carbohydrate diet for 5 d (Figure 1⇓; P < 0.05).

(And one thing to note - this study's "low carb diet" was 45% of calories from carbs - which is anything but low carb the way the low carb community would define it. Atkins induction is less than 5% of calories from carbs, and I'd be willing to guess that at that level, DNL would be minimal even for those who were hyper-insulinemic.)

33 posted on 06/08/2013 12:51:55 PM PDT by jdege
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To: napscoordinator

??? You being a prick or something?
How fat and unhealthy are you?
Can you ride 80 miles per week?
IOW screw yourself!


34 posted on 06/08/2013 2:31:29 PM PDT by poobear (Socialism in the minds of the elites, is a con-game for the serfs, nothing more.)
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Comment #35 Removed by Moderator

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