How much phenylalanine?

Aspartame: "In the synthesis of aspartame, the starting materials are a racemic mixture (equal quantities of both isomers) of phenylalanine, and aspartic acid."

So, about half. And Diet Pepsi contains about 124 mg of aspartame per 355 ml bottle. That makes it about 62 mg of phenyalanine per 11.8 ounce bottle. A big refillable cup of about 32 ounces then would net you about 180 mg.

Phenylalanine administration influences dopamine release in the rat's corpus striatum

Entrez PubMed: "A dose of 200 mg/kg phenylalanine increased basal dopamine release by 59%, peaking at 75 min. There was no change in basal dopamine release after the 500 mg dose, whereas the 1000 mg/kg dose significantly reduced (26%) dopamine release. No significant changes were observed in the concentrations of DOPAC and HVA with any of the treatments, indicating that changes in brain phenylalanine and tyrosine levels may selectively affect production of the dopamine molecules that are preferentially released into synapses."

Phenylalanine is a component of aspartame or Nutrasweet. I thought we did studies on rats so we could extrapolate data for human use.

Dopamine Transporter Tryptophan Mutants Highlight Candidate Dopamine- and Cocaine-Selective Domains

Lin et al. 58 (6): 1581 -- Molecular Pharmacology: "Dopamine transport has been modeled as involving a number of discrete steps likely to involve many different domains of the DAT protein. These could include sodium, dopamine, and chloride recognition by an 'outward facing' transporter state, dopamine and ion translocation, intracellular unloading of dopamine and ions, and return of the unloaded carrier to its extracellular-facing state (Povlock and Schenk, 1997). DAT's turnover rate for dopamine could be influenced by mutations that altered any of these processes. Interestingly, dopamine turnover was altered by a higher fraction of the normally expressed DAT tryptophan mutants, 43%, than the fraction at which mutations alter affinities for either dopamine or CFT. Proline, phenylalanine, and aspartic acid mutant series also displayed prominent alterations in turnover number: 41% of phenylalanine substitutions display turnover number changes, although the maximal magnitude of the change is larger for the phenylalanine mutants "

Man, I wish I could figure out what all of that meant! :)

Behavioural and biochemical effects of tryptophan, tyrosine and phenylalanine in mice

SpringerLink - Journal Article: "Tyrosine decreased immobility in the swim test and markedly increased activity in the open field test, an action similar to the psychostimulants amphetamine and caffeine. Phenylalanine decreased immobility in the swim test, but did not affect open field activity. Thus, its behavioural effects are similar to those of an antidepressant. As expected, tryptophan increased brain tryptophan and serotonin in a dose-related fashion. Tyrosine did not alter dopamine or noradrenaline levels, while phenylalanine lowered dopamine, noradrenaline and serotonin."

Whoa, now ... phenylalanine has the behavioural effect of an anti-depressant but a blood-level effect that simulates depression?

Effects of phenylalanine on the release of endogenous dopamine from rat striatal slices

Entrez PubMed: "We conclude that phenylalanine is a less effective precursor of DA in rat striatum than tyrosine and that it can also act to inhibit DA synthesis, depending on its concentration." - J Neurochem. 1986 Nov;47(5):1444-8.

Now I'm looking at the studies to back up a phenylalanine-dopamine connection.

The Diet Pepsi connection

Fox, Michael J.: "He was a blur. That's how I remember Michael J. FOX the first time we talked. It was 1987. I'd come to Los Angeles to interview him for a Maclean's cover story, and we met at a Family Ties rehearsal at Paramount. He bounced around the set like a hyperactive kid, cranking Diet Pepsi, and kept ducking out to smoke Export 'A's, lighting one off the other. During a break, we hopped into his black Ferrari for a quick trip to his house halfway across town, and he tore down the Hollywood Freeway at twice the speed limit, his seat belt unbuckled, the dashboard dusty with cigarette ash, the floor of the car littered with beer cans." - an excerpt from a Maclean's interview with Michael

I'm just looking up sites that mention Michael's heavy use of Diet Pepsi, for future reference. I had heard it batted around as a potential cause of Parkinson's but didn't really dig into it or anything.

from the New England Journal of Medicine

A Randomized Trial of Multivitamin Supplements and HIV Disease Progression and Mortality: "Results Of 271 women who received multivitamins, 67 had progression to World Health Organization (WHO) stage 4 disease or died — the primary outcome — as compared with 83 of 267 women who received placebo (24.7 percent vs. 31.1 percent; relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.98; P=0.04). This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome (0.73; 95 percent confidence interval, 0.51 to 1.04; P=0.09), progression to WHO stage 4 (0.50; 95 percent confidence interval, 0.28 to 0.90; P=0.02), or progression to stage 3 or higher (0.72; 95 percent confidence interval, 0.58 to 0.90; P=0.003). Multivitamins also resulted in significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads. The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo. Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined. "

So, multivitamins increased longevity and/or survival over placebo by 6.4%.

AIDS reappraisal movement

Here's one summary of the movement from Wikipedia.

Doctors Find AIDS-Like Disease Without H.I.V. Virus Is Growing - New York Times

New York Times: "European and American doctors added new reports today to earlier descriptions of patients with an AIDS-like disease but no detectable evidence of infection with H.I.V., the virus that causes AIDS.

The reports raised several possibilities. The new condition, reported in about 30 patients, may be caused by a third variant of H.I.V. Or it may be a deficiency of the immune system caused by some other condition or agent. The new agent might be a microbe or some environmental factor.

American health officials appealed to doctors today to report any similar cases to the Federal Centers for Disease Control. They said the case reports would be used in an intense effort to determine precisely what factors were shared by the men and women with the AIDS-like illness. They said the cases might not be linked. 5 Cases Described

Several researchers have said privately that they believe they have found evidence that patients with the mysterious condition have been infected with previously unidentifed microbes or mutants of H.I.V., the virus that causes AIDS. But they have not formally reported their findings.

If a new microbe is involved, a screening test to protect the blood supply can be developed after it is isolated, the health officials said.

'We do not know of any evidence of transmissibility,' Dr. James Allen, who directs the National AIDS Program Office in Washington, said at a news conference. He said that because the mysterious cases are rare and because the blood supply is subjected to rigorous testing, transfusions are safer today than ever.

But Dr. James Curran, an AIDS expert at the Centers for Disease Control in Atlanta, said here it was not clear whether the known cases represent a new syndrome or a variety of rare medical problems that pose no threat to the nation's health. It is also possible that some longstanding, rare disease of the immune system is being identified now because doctors concerned about AIDS are giving new attention to their patients' immune systems."

Note that this is a news article from 1992.

A Closer Look FAQ's : Proof that HIV Causes AIDS?

Proof that HIV Causes AIDS?: "Since the 28 AIDS-defining illnesses are only defined as AIDS when they happen to people who test HIV positive, it's clear why there would be a 100% correlation between HIV and AIDS. These diseases can only be called AIDS when they happen to someone labeled HIV positive even though they can and do occur in people considered HIV negative. This circular logic renders the argument 'HIV causes AIDS because it's present in 100% of AIDS cases' meaningless. The 100% correlation between HIV and AIDS is an artifact of the definition of AIDS. Here is one example you may wish to use for your debate: Tuberculosis (TB) is a serious health threat to impoverished people in the US and to the populations of many developing countries. Worldwide, TB takes millions of lives every year. Although TB is caused by mycobacteria tuberculosis and not by HIV, since 1987, people with TB who also test positive on an 'HIV test' receive a diagnosis of AIDS. As you may know, TB existed prior to its inclusion as an AIDS-defining illness in 1987 and was described in the medical literature in the early 1900s.

To further clarify the point of the circular definition, take a look at cervical cancer and candida. These AIDS-defining conditions are commonly found among people in non-AIDS risk groups who do not 'have HIV.' Despite the fact that over 90% of women with cervical cancer are not HIV positive, cervical cancer is called AIDS in women who do test HIV positive. Although 30% of all Americans are thought to suffer from chronic candida (John Hightower, MD 'The Yeast Connection') and candida is caused by a bacterial imbalance, not HIV, candida is called AIDS in a person who tests HIV positive."

What Causes AIDS?

HIV & AIDS - What Causes AIDS?: "While HIV infection remains steady at this modest level in the United States, World Health Organization officials claim that the same virus is spreading rapidly in Africa and Asia, creating a vast 'pandemic' that threatens to infect at least 40 million people by the year 2000, unless billions of dollars are provided for prevention to the organizations sounding the alarm. These worldwide figures, especially from Africa, are used to maintain the thesis that 'everyone is at risk' in the United States. Instead of telling Americans that AIDS cases here are almost 90-percent male, authorities say that worldwide the majority of AIDS sufferers are female. With the predictions of a mass epidemic in America and Europe failing so dramatically, AIDS organizations rely on the African figures to vindicate their theory.

But these African figures are extremely soft, based almost entirely on 'clinical diagnoses,' without even inaccurate HIV testing. What this means in practice is that Africans who die of diseases that have long been common there---especially wasting disease accompanied by diarrhea-are now classified as AIDS victims. Statistics on 'African AIDS' are thus extremely manipulable, and witnesses are emerging who say that the epidemic is greatly exaggerated, if it exists at all.

In October 1993, the Sunday Times of London reported on interviews with Philippe and Evelyne Krynen, heads of a 230-employee medical relief organization in the Kagera province of Tanzania. The Krynens had first reported on African AIDS in 1989 and at that time were convinced that Kagera in particular was in the grip of a vast epidemic. Subsequent years of medical work in Kagera have changed their minds. They have learned that what they had thought were 'AIDS orphans' were merely children left with relatives by parents who had moved away and that HIV-positive and HIV-negative villagers suffer from the same diseases and respond equally well to treatment. Philippe Krynen's verdict: "There is no AIDS. It is something that has been invented. There are no epidemiological grounds for it; it doesn't exist for us."

Krynen's remark calls attention to the fact that AIDS is not a disease. Rather, it is a syndrome defined by the presence of any of 30 separate and previously known diseases, accompanied by the actual or suspected presence of HIV. The definition has changed over time and is different for Africa (where HIV testing is rare) than for Europe and North America. The official CDC definition of AIDS in the United States was enormously broadened for 1993 in order to distribute more federal AIDS money to sick people, especially women with cervical cancer. As a direct result, AIDS cases more than doubled in 1993. Absent the HIV mystique, there would be no reason to believe that a single factor is causing cervical cancer in women, Kaposi's sarcoma in gay males, and slim disease in Africans. "