Montag, 29. April 2013

Cliffnotes on Vegetarianism and Diet in general: The Big Picture

I know how unbelievably hard it is not just to parse research, since there is so much of it, but also to understand its implications. Over time I have gotten better at this, but it does take practice. Here, I will try to put current research into context and given how popular paleo-style diets are, I will also address this issue. I think a pattern is emerging:

Ramsden et al. 2013 (2) extended their older meta-analysis that found n6 polyunsaturated fats (PUFA) to be at best health-neutral and possibly harmful. Yes, this seems to be a "win" for the paleo-diet in a sense, but better scientific arguments against excessive n6 PUFA intakes existed for a long time. For instance, a simple argument based on oxidative stress.

Notably, the next few studies are inconsistent with the "paleo-hypothesis":

The huge PREDIMED trial (3) showed that the addition of two plant foods: tree nuts and even more so virgin olive oil (EVOO) is beneficial in primary prevention; laying the foundation for Mediterranean-style moderate-to-high-fat vegetarianism. Consistent with Ramsden et al. EVOO performed slightly better!

(As a side note: There is still no good research linking moderate fructose intakes to bad health outcomes. )

Huang et al. 2012 (1) re-confirmed an older meta-analysis that found modestly reduced mortality in vegetarians.

Another research group  found a novel mechanism which may explain how and why meat is harmful to health. (4) This year the group extended their research on trimethylamines (TMA or TMAO) that gut microbiota could produce from meat constituents.

The only reasonable conclusion
Three very high impact papers (1-3) have produced concordant results. If we combine the data we are able to confirm that Mediterranean-style (3) vegetarianism (1) that emphasizes MUFA from olive oil, and to some extent "balanced" n3 and n6 from nuts over saturated fats and n6 PUFA (2), produces the best health outcomes.

This dietary recommendation rests on a sound foundation of basic (e.g. ref. 4) and translational research when compared with the classical low-fat food pyramids. Evidently, some questions need to be answered but this should not affect the above recommendation.

Just to be clear: I do endorse flexible vegetarianism. In the end it is all about your average long term intake.

(1) Ann Nutr Metab. 2012;60(4):233-40. doi: 10.1159/000337301. Epub 2012 Jun 1.
Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review.
Huang T, Yang B, Zheng J, Li G, Wahlqvist ML, Li D.

*(2) BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707.
Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.
Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR.

(3)  Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013; DOI: 10.1056/NEJMoa200303.

*(4) Nat Med. 2013 Apr 7. doi: 10.1038/nm.3145. [Epub ahead of print]
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis.
Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL.

*papers I have not yet read in full, although, I am familiar with earlier work. Hope I can blog on this in the future

Samstag, 27. April 2013

The Plot Thickens

Polyunsaturated fatty acids in and of themselves may be unhealthy. Evidence to that effect has been trickling in for some time now. I hope I will be able to read the paper soon and then comment on it.

BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707.
Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis.
Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR.

To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death.

Evaluation of recovered data from the Sydney Diet Heart Study, a single blinded, parallel group, randomized controlled trial conducted in 1966-73; and an updated meta-analysis including these previously missing data.

Ambulatory, coronary care clinic in Sydney, Australia.

458 men aged 30-59 years with a recent coronary event.

Replacement of dietary saturated fats (from animal fats, common margarines, and shortenings) with omega 6 linoleic acid (from safflower oil and safflower oil polyunsaturated margarine). Controls received no specific dietary instruction or study foods. All non-dietary aspects were designed to be equivalent in both groups.

All cause mortality (primary outcome), cardiovascular mortality, and mortality from coronary heart disease (secondary outcomes). We used an intention to treat, survival analysis approach to compare mortality outcomes by group.

The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6% v 11.8%, hazard ratio 1.62 (95% confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2% v 11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3% v 10.1%, 1.74 (1.04 to 2.92), P=0.04). Inclusion of these recovered data in an updated meta-analysis of linoleic acid intervention trials showed non-significant trends toward increased risks of death from coronary heart disease (hazard ratio 1.33 (0.99 to 1.79); P=0.06) and cardiovascular disease (1.27 (0.98 to 1.65); P=0.07).

Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.

Clinical trials NCT01621087.

Samstag, 13. April 2013

The Hypothalamus and Aging

The hypothalamus regulates lots of things including satiety (esp. lateral and ventromedial hypothalamus), temperature and many hormones relevant to aging.

Seriously, why has no one performed these studies? At least not to my knowledge:
This review compares outcomes of lesions in the VMN, DMN [ventro- and dorsomedial nucleus], and lateral hypothalamic area (LHA) for relevance to aging. To establish a relationship between these anatomic areas of the hypothalamus and aging, it is concluded that the VMN, DMN, and LHA lesions should be examined for impact on longevity and compared with data obtained from simultaneously studied intact ad-lib-fed and 40% calorie-restricted animals. Lesioned animals also should be rigorously studied for neurotransmitters (e.g., neuropeptide Y, beta-endorphin, serotonin, corticotropin-releasing factor, and galanin), and for behavioral changes consistent with aging, for accumulation of specific tissue lipofuscin and amyloid that are associated with normal aging and for other age-dependent findings, such as incidence of tumors and cataract.

Physiol Behav. 1996 Mar;59(3):523-36.
Aging and the hypothalamus: research perspectives.
Bernardis LL, Davis PJ.

Montag, 8. April 2013

Fructose: friend or foe? Preliminary findings.
This discussion has been going on for quite some time and it is certainly not limited to the lay press and lay population. I have always been interested in double checking pop-sci claims, in this case the "evil fructose" meme.

First, I would like to emphasize that the available evidence does not change the basic Public Health Message: Yes, you should still eat more fruits unless you are already getting more than five servings/day. In that case you probably want to get more vegetables or olive oil, since a varied, plant-based Mediterranean-style diet remains the best option for health.

On to the hard science:

As of today, and as far as primary prevention is concerned, the studies I want to discuss (1-4) are only relevant for "dietary perfectionists", researchers and interested laypeople. The data is so weak and preliminary, I already feel like I am jumping the gun with my conclusions based on my ongoing, but superficial review of the data. Nevertheless I feel like sharing my hypothesis.

Reasonable fructose intakes (<60g/d) may be beneficial for cardiometabolic risk factors summa summarum (1, 2) or at the very least neutral. It has been speculated that catalytic fructose doses, below approx. 10g, free up intracellular glucokinase ("hexokinase") thereby increasing glycolytic flux. This could lower blood glucose after meals.

I am still unclear on longterm fructation vs. glycation, and their impact on aging and health. Instead I would like to highlight a different issue. Fructose and pancreatic cancer (3). Dr. "ORAC" has explained the basics if you long for an accessible review.