Thursday, March 08, 2007

Folate rots elderly brains

But only if the person is low on B12. That is, however, common

To protect the offspring of folate-deficient mothers against neural tube defects, the US diet has been fortified with folic acid since 1998, and this vitamin is also widely consumed in multivitamin supplements. Folic acid and vitamin B-12 share metabolic interactions, and there is concern that excessive folic acid could be harmful in elderly people, who are at increased risk of vitamin B-12 deficiency with attendant cognitive defects and anemia.

Publishing in this month's American Journal of Clinical Nutrition, Morris and colleagues at the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University in Boston, MA, assessed the potential risks of excessive folic acid in more than 1000 elderly subjects who had provided data to the 1999-2002 US National Health and Nutrition Examination Survey (NHANES). The mean age of the subjects was 70 years, and two-thirds took dietary supplements.

Of the group, 21% had high folate status with serum folate concentrations > 59 nmol/L, and 25% had low vitamin B-12 status with low serum vitamin B-12 concentrations (<148 pmol/L) and/or elevated methylmalonic acid (>210 nmol/L). Standardized testing identified cognitive impairment in 32% of the group with low vitamin B-12 status compared with 15% in the group with normal vitamin B-12 status.

Compared with subjects with normal vitamin B-12 and folate status, those with high folate and normal vitamin B-12 status were protected against both anemia and cognitive defect with odds ratios of 0.6 and 0.56, respectively. By contrast, the odds ratios for anemia and cognitive defect in those with low vitamin B-12 and normal folate status were 2.0 and 1.9, respectively, and increased to 5.2 and 4.9 in those with low vitamin B-12 and high folate status (4% of all subjects).

Thus, folic acid fortification and supplementation may have deleterious consequences in a significant number of elderly US subjects. An accompanying editorial by Smith points to several other studies showing that folic acid fortification and supplementation contribute to high concentrations of unmetabolized circulating folic acid in about 80% of people, whereas high folate concentrations were associated in one study with an increased risk of colon cancer and in another with decreased immune function due to a decrease in the effectiveness of natural killer cells.

In view of the large number of elderly subjects at risk of vitamin B-12 deficiency, Smith poses the public health question whether the routine use of folic acid fortification and supplementation carries a much greater risk of cognitive decline and anemia in the elderly than the potential benefit of protection against neural tube defects in infants.


Journal abstract follows:

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

By Martha Savaria Morris et al.

Background: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical.

Objective: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey.

Design: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration <148 pmol/L or a serum methylmalonic acid concentration >210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine.

Results: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate >59 nmol/L (80th percentile), as opposed to ~ 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were <1.0 (Pinteraction < 0.05), but significantly <1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9).

Conclusion: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.


In mice and in the test tube

A combination of an anti-arthritis drug and green tea could slow the growth of prostate cancer, scientists say. American researchers have previously shown both celecoxib, sold as Celebrex, and a chemical in green tea called pigallocatechin-3-gallate (EGCG) can independently reduce the progression of prostate tumours in laboratory animals. Experiments have shown that while tumours in mice given one or the other substance grow at around half the normal speed, those in mice given both spread at about a quarter of the usual rate.

Hasan Mukhtar, professor of dermatology at the University of Wisconsin-Madison, said: "Celecoxib and green tea have a synergistic effect - each triggering cellular pathways that, combined, are more powerful than either agent alone. "If tests in human trials replicate these results, we could see a powerful combined therapy that is both simple to administer and relatively cost effective." Prof Mukhtar's research was published yesterday in the journal Clinical Cancer Research.

Celecoxib, one of a group of drugs called Cox-2 inhibitors, is usually used by osteoarthritis and rheumatoid arthritis sufferers to relieve joint pain, stiffness and swelling. Last year a study found those taking high doses for long periods were at more than twice the normal risk of suffering a heart attack.

Prof Mukhtar said: "Our studies showed that the additive effect of green tea enables us to utilise the cancer-fighting abilities of Cox-2 inhibitors, but at lower, safer doses."


Abstract follows:

Combined Inhibitory Effects of Green Tea Polyphenols and Selective Cyclooxygenase-2 Inhibitors on the Growth of Human Prostate Cancer Cells Both In vitro and In vivo

By Vaqar Mustafa Adhami et al.

Purpose: Cyclooxygenase-2 (COX-2) inhibitors hold promise for cancer chemoprevention; however, recent toxicity concerns suggest that new strategies are needed. One approach to overcome this limitation is to use lower doses of COX-2 inhibitors in combination with other established agents with complementary mechanisms. In this study, the effect of (-)epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent from green tea, was tested alone and in combination with specific COX-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo.

Experimental Design: Human prostate cancer cells LNCaP, PC-3, and CWR22Rv1 were treated with EGCG and NS398 alone and in combination, and their effect on growth and apoptosis was evaluated. In vivo, athymic nude mice implanted with androgen-sensitive CWR22Rv1 cells were given green tea polyphenols (0.1% in drinking water) and celecoxib (5 mg/kg, i.p., daily, 5 days per week), alone and in combination, and their effect on tumor growth was evaluated.

Results: Combination of EGCG (10-40 ‘mol/L) and NS-398 (10 ‘mol/L) resulted in enhanced (a) cell growth inhibition; (b) apoptosis induction; (c) expression of Bax, pro-caspase-6, and pro-caspase-9, and poly(ADP)ribose polymerase cleavage; (d) inhibition of peroxisome proliferator activated receptor kB compared with the additive effects of the two agents alone, suggesting a possible synergism. In vivo, combination treatment with green tea polyphenols and celecoxib resulted in enhanced (a) tumor growth inhibition, (b) lowering of prostate-specific antigen levels, (c) lowering of insulin-like growth factor-I levels, and (d) circulating levels of serum insulin-like growth factor binding protein-3 compared with results of single-agent treatment.

Conclusions: These data suggest synergistic and/or additive effects of combinatorial chemopreventive agents and underscore the need for rational design of human clinical trials.


Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.